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Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2015

Mechanism of β-lactam action in Streptococcus pneumoniae: the piperacillin paradox

Résumé

The human pathogen Streptococcus pneumoniae has been fought for decades with β-lactam antibiotics. Resistance is now widespread, mediated by the expression of mosaic variants of the target enzymes, the penicillin-binding proteins or PBPs. Understanding the mode of action of β-lactams, not only in molecular details, but also in their physiological consequences, will be crucial to improve these drugs and counter resistance. In this work, we investigate the piperacillin paradox, by which this β-lactam selects primarily variants of PBP2b, whereas its most reactive target is PBP2x. These PBPs are both essential mono-functional transpeptidases involved in peptidoglycan assembly. PBP2x participates to septal synthesis, while PBP2b functions in peripheral elongation. The formation of "lemon"-shaped cells induced by piperacillin treatment is consistent with the inhibition of PBP2x. Following the examination of treated and untreated cells by electron microscopy, localization of the PBPs by epifluorescence microscopy, and determination of the inhibition time-course of the different PBPs, we propose a model of peptidoglycan assembly that can account for the piperacillin paradox.

Domaines

Bactériologie

Dates et versions

hal-01093880 , version 1 (11-12-2014)

Identifiants

Citer

Jules Philippe, Benoit Gallet, Cécile Morlot, Dalia Denapaite, Regine Hakenbeck, et al.. Mechanism of β-lactam action in Streptococcus pneumoniae: the piperacillin paradox. Antimicrobial Agents and Chemotherapy, 2015, 59, pp.609-621. ⟨10.1128/AAC.04283-14⟩. ⟨hal-01093880⟩
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